Transplantation of functional cells and tissues from a donor individual into a recipient is a major means of replacing failing or non-functional organs or tissues in the recipient. One of the major obstacles to successful transplantation is rejection of the transplanted cells or tissues by the recipient's immune system, due to tissue incompatibility. Immunosuppressive drugs such as cyclosporin A are currently used to reduce transplant rejection. However, immunosuppressive drugs are costly, toxic, and sometimes ineffectual. In humans, molecules encoded by the human leukocyte antigen (HLA) locus provide the context for the recognition of “non-self” or foreign cells by the transplant recipient.
The histocompatibility type of an individual is determined by many genes located in the HLA locus on human chromosome 6. Every person has two copies of the HLA locus—one on each copy of chromosome 6. There are several different versions or “haplotypes” of the genes in the HLA locus, and since there are two copies of each gene, it is very unlikely that two individuals have the same versions of each gene or “HLA type.”
To ensure that transplants, such as bone marrow transplants, are not rejected by a recipient, attempts are made to use a donor with the same HLA type. The chances that a prospective recipient's sibling will have the same HLA type as the recipient are about 1 in 4. Therefore, siblings are usually used as donors when performing bone marrow transplantation. If no HLA-matched sibling is available, then an unrelated, HLA-matched, donor can sometimes be found; however, this requires searching through thousands of potential donors in the unrelated bone marrow donor registry to find an HLA match. More typically, where an unrelated donor is used, an exact match is not found; instead, a near-match is used.
In solid organ transplantation, HLA matching is typically not possible, due to the limited number of donors. Because organ transplantation typically involved HLA unmatched donors and recipients, aggressive immunosuppressive medications are typically required. These medications are very toxic and often fail to prevent transplant rejection.
There is an ongoing need in the art for HLA matched stem cells that can serve as donors in various therapeutic transplant settings.
Literature
U.S. Pat. No. 7,030,292; WO 98/48005; U.S. Pat. No. 6,986,887.